Antipsychotics are related to psychometric conversion to psychosis in ultra‐high‐risk youth

Abstract

Background The prescription of antipsychotics outside overt psychotic conditions remains controversial, especially in youth where it is relatively widespread. Furthermore, some studies seem to indicate that antipsychotic exposure in individuals at ultra‐high‐risk (UHR) for psychosis is associated with higher conversion rates. This study was set up to test whether the inter‐current prescription of antipsychotics in UHR patients was related to the psychometric threshold for a diagnosis of psychosis. Methods The 24‐item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 125 UHR participants. Standard psychometric criteria were used to quantify conversion to psychosis. Kaplan‐Mayer and Cox proportional hazard survival analysis were applied to determine the impact of having or not received the prescription of an antipsychotic drug. Results Over the study period 30 (24%) subjects received the prescription of an antipsychotic. In the sample, there were 31 participants (25%) who had reached the psychometric threshold for conversion to psychosis after 2 years of treatment. UHR people who received a prescription of antipsychotics during the first 2 years of treatment were statistically more likely to reach the psychometric threshold for conversion to psychosis on the BPRS: Hazard ratio = 3.03 (95%CI: 1.49–6.16); p = .003. Conclusion This finding supports the hypothesis that the prescription of antipsychotics within UHR cohorts is to be considered a red flag for higher incipient risk of conversion to psychosis.

Baseline antipsychotic prescription and short‐term outcome indicators in individuals at clinical high‐risk for psychosis: Findings from the Parma At‐Risk Mental States (PARMS) program

“…Overall, these findings suggest that baseline AP exposure may be considered as a simple warning 'flag' for a higher incipient risk of psychosis and for other poor short-term outcomes (such as new hospitalization, more urgent/non-planned visits) as compared to AP-naive In conclusion, in agreement with increasing empirical evidence (Preti et al, 2022;Raballo et al, 2020b;Zeng et al, 2022), the current study suggests that AP need is a significant prognostic variable in cohorts of CHR-P individuals and should be included in the current risk calculators. In particular, the results of this study conducted in a realworld clinical setting indicate that the rate of CHR-P individuals who were already exposed to AP at the time of CHR-P status ascription was higher than those reported in recent meta-analyses on this topic (Raballo et al, 2020b(Raballo et al, , 2021b.…”

“…This finding is substantially in line with what was found in a recent meta-analysis (reporting an overall 29% vs. 16% at 1-year follow-up) (Raballo et al, 2020b) and in recent single-cohort studies (reporting 47% vs. 18% at 2-year follow-up and T A B L E 4 Logistic regression of dichotomized T1 hospitalization condition by clinical and sociodemographic characteristics after the 1-year follow-up period in the CHR-P total group (n = 178). 27.0% vs. 10.9% at 3-year follow-up) (Preti et al, 2022;Zeng et al, 2022). Overall, these results suggest that in many of the severe CHR-P cases (as indicated by an increased baseline clinical severity…”

Do antidepressants prevent transition to psychosis in individuals at clinical high-risk (CHR-P)? Systematic review and meta-analysis

“…Unfortunately, the source studies included in the current meta-analysis only reported the crude information on whether a patient was under AD treatment at baseline and not whether and for how long it was maintained during the follow-up, therefore it was not possible to perform subtler analyses on the timing and extension of AD effect. This is a limitation that could be overcome only by a more detailed, comprehensive and transparent description of the samples (Preti et al, 2021;Raballo et al, 2020bRaballo et al, , 2021b, which is an important prerequisite to support precision psychiatry (Raballo et al, 2021a;Sanfelici et al, 2020). It is worth noting that in the North American Longitudinal Prodrome Study 2 (NAPLS-2), the lifetime months of exposure to baseline medications was 18 months for antidepressants (Woods et al, 2013), which is enough to produce a tangible therapeutic effect.…”

“…Crucially, such an effect is not due to differences in pretest risk enrichment across the studies (Raballo, Poletti, & Preti, 2021b). Multiple potential causes can be hypothesized for this negative prognostic effect, including harmful effects of antipsychotics (Zhang et al, 2020) and dopamine super-sensitivity induced psychosis (Chouinard et al, 2017) as well as artifactual ascription to CHR-P of individuals actually undergoing an unrecognized first episode psychosis contingently mitigated by AP treatment (Raballo & Poletti, 2019; Raballo, Poletti, & Preti, 2020b); in any case, it is clear that ongoing AP treatment in newly identified CHR-P individuals is a clinical red flag for more imminent risk of transition to psychosis (Preti et al, 2021; Raballo, Poletti, & Preti, 2021c).…”

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

“…It should be noted that in CHR-P individuals, baseline exposure to antipsychotics is associated with a greater risk of transition to psychosis both at a meta-analytical level (Raballo et al, 2020b; Raballo, Poletti, & Preti, 2023) and in subsequent field testing and reanalysis of available cohorts (Preti et al, 2022; Zhang et al, 2022), and it might be that BDZ – although this info is omitted in the source literature - could have been co-administered with antipsychotics, thereby capturing part of the AP-related pro-transition effect.…”